0125 GMT May 25, 2019
Some carriers may experience social deficits and milder versions of cognitive and behavioral disorders associated with full-blown fragile X syndrome. These include autism spectrum, attention deficit hyperactivity, and mood and anxiety disorders, HealthCanal said.
Researchers at Washington University School of Medicine in St. Louis have identified a potential target for treatments for fragile X carriers. This population includes 1 million women and 320,000 men in the United States, according to a 2012 study led by the Centers for Disease Control and Prevention.
"Full-blown fragile X syndrome eliminates the body's ability to make a key brain protein," explained Azad Bonni, MD, PhD, the Edison Professor of Neurobiology and head of the Department of Anatomy and Neurobiology at the School of Medicine. "In contrast, carriers of the mutation make the protein but produce significantly less of it than people without the mutation. We've just identified a potential way to boost levels of this protein. This ultimately could lead to treatments to ease the carriers' symptoms."
Bonni was studying an enzyme known as Cdh1-APC when several clues suggested it might be linked to the fragile X protein. He investigates Cdh1-APC because of its role in shaping the growth and structure of nerve cells.
He and his colleagues knocked out Cdh1-APC in mice and then looked at a single, well-studied synapse between a pair of nerve cells in the hippocampus, a structure of the brain that is important for learning and memory. They found that an adjustment of the signaling process across synapses was changed.
"Nerve cells use a phenomenon called plasticity to encode memory by altering the ease with which they send signals to each other," he said. "One form of plasticity is called long-term depression. At the synapse we studied in the hippocampus, this form of plasticity was disabled when we knocked out Cdh1-APC."